The research is directed towards determining the chemical nature of the stimulus that induces precursor antibody-forming cells to mature to antibody-forming cells. Precursor cells appear to require two signals for activation, the first delivered via antigen binding to surface immunoglobulin receptors, and the second via the interaction of a cooperating cell type with precursor cells. The nature of the cooperating cell type and the manner in which a signal is delivered to precursor cells is being analyzed. The biochemical changes that take place in precursor cells following signal delivery appear to fall into two categories: the antigen-receptor interaction may activate adenyl cyclase activity in precursor cells raising intracellular levels of cyclic AMP, whereas the cooperating cells may activate guanyl cyclase activity in precursor cells. The phenotypic expression of precursor cells may be controlled by the intracellular ratio of cyclic AMP:cyclic GMP.